653. Myeloma/Amyloidosis: Therapy, excluding Transplantation; Novel Approaches for Relapsed/Refractory Myeloma and Amyloidosis

Niels W.C.J. Van De Donk, Rakesh Popat, Jeremy Larsen, et al.

Authors Conclusion from the Abstract: IberDd and IberVd showed a favorable tolerability profile in heavily pretreated RRMM pts, with promising clinical activity, even among pts refractory to the last prior regimen and previously exposed to IMiD agents, PIs, and CD38 antibodies. Immune-profiling data confirm that IBER + DEX was pharmacodynamically active in triplet combination and not augmented by the addition of DARA or BORT. The study is ongoing with continued enrollment at the 1.6 mg dose level for both cohorts. Updated results, including the MTD/RP2D, will be presented at the meeting. These results support the further development of IBER-based regimens in MM; phase 3 trials are planned to further evaluate these combinations.

Suzanne Trudel, Arleigh McCurdy, Heather J Sutherland, et al.

Authors Conclusion from the Abstract: The results show promising efficacy. The TEAEs were acceptable and consistent with the known safety profiles for belamaf and POM. However, the high rate of dose holds at the 2.5 mg/kg dose has prompted exploration of alternative dosing schedules that are enrolling and will be presented. The RP2D selection is pending completion of the current cohorts.

Christine I Chen, Nizar Bahlis, Cristina Gasparetto, et al.

Authors Conclusion from the Abstract: The RP2D is SEL 60 mg QW, POM 4 mg QD and dex 40 mg QW. The ORR was 58% in pts in LEN treated or refractory and POM naïve MM compared to previously published data of 31% ORR with Pd in a similar population. The median PFS on SPd of 12.3 months in POM naïve pts is longer than that historically observed with Pd (~4 months). All TRAEs were expected and manageable with appropriate supportive care (eg, G-CSF) and/or dose modifications. The all oral SPd combination appears to confer relatively high ORR with good durability and promising PFS in pts with heavily pretreated MM.

Yael C Cohen, Mor Zada, Shuang-Yin Wang, et al.

Authors Conclusion from the Abstract: In summary, our study defines a roadmap for combining single cell RNA-seq profiling with clinical trials. We reveal and externally-validate a novel transcriptional signature for therapy resistance. We show inhibition of PPIA, a potential target identified, by CsA, overcomes relative resistance of MM cell lines to carfilzomib. We anticipate that such studies will significantly improve the ability to define mechanism of action of treatment, molecularly characterize the Pts that may benefit from the treatment, and reveal potential novel targets.

Terri L. Parker,  Adam Rosenthal, Vaishali Sanchorawala, et al.

Authors Conclusion from the Abstract: Isatuximab demonstrates encouraging efficacy in previously treated patients with AL amyloidosis. The administration of isatuximab in these patients is associated with a good safety profile similar to other monoclonal antibodies against CD38. The data will be updated at the meeting.

Jack Khouri, Faiz Anwer, Christy J. Samaras, et al.

Authors Conclusion from the Abstract: CAEL-101 dosed at 1000 mg/m2 is the recommended phase 3 dose in combination with CyBorD for upcoming randomized, double blind, phase 3 trials. Hematologic responses do not seem to be affected by concurrent use of CAEL-101 with CyBorD. Organ responses have occurred early in the course of therapy and are expected to increase over time, particularly after completion of chemotherapy and dexamethasone. Longer follow up, the ongoing exposure to CAEL-101 after the conclusion of chemotherapy and planned phase III trials will provide more data on organ response, quality of life and survival.